Abstract

Background

Eligibility is often narrowed in clinical trials of targeted drugs because of specific adverse effects. Modified eligibility criteria can affect endpoints such as overall survival independently of the actual effect of an investigational drug.

Methods

Patients with stage IIIB/IV, non-squamous non-small cell lung cancer (NSCLC) who started chemotherapy from 2005 to 2009 were reviewed. Bevacizumab (BV) was first used to treat lung cancer at our institution in 2010. We divided patients into BV-eligible (A) and -ineligible (B) groups. To estimate survival, Kaplan-Meier curves were calculated and compared between the groups using the log-rank test. We also examined the prognostic impact of age, gender, M factor, performance status (PS), use of platinum in first-line chemotherapy, history of hemoptysis, major blood vessel invasion (MVI) by the tumor and clinically significant cardiovascular disease upon overall survival using the Cox proportional hazards model. A radiologist who was blinded to the clinical outcomes evaluated MVI. All tests were two sided with a significance level of 0.05.

Results

Among 576 patients with lung cancer who undergone chemotherapy at our department, 283 of them had stage IIIB/IV non-squamous NSCLC. After excluding 15 patients with indications for combined chemoradiotherapy and 22 with PS 3/4, the eligibility of 246 patients for BV was finally evaluated. Eighty-nine patients were considered ineligible for BV (cohort B), based on one or more of a history of hemoptysis (N = 32), MVI (N = 64) and cardiovascular disease (N = 13). Eligibility could not be determined in ten patients and the remaining 147 patients were classified into cohort A. Overall survival was significantly better in cohort A (median, 14.9 months) than in cohort B (median, 8.6 months; hazard ratio, 0.55; 95%CI, 0.42-0.74; P < .0001). Multivariate analysis indicated that gender, PS, a history of hemoptysis and MVI are significant prognostic factors.

Conclusion

Eligibility for BV itself is a powerful prognostic factor for patients with non-squamous NSCLC.